Medical devices may be coated so that the surfaces of such devices have desired properties or effects. For example, it may be useful to coat medical devices to provide for the localized delivery of therapeutic agents to target locations within the body, such as to treat localized disease (e.g., heart disease) or occluded body lumens. Localized drug delivery may avoid some of the problems of systemic drug administration, which may be accompanied by unwanted effects on parts of the body which are not to be treated. Additionally, treatment of the afflicted part of the body may require a high concentration of therapeutic agent that may not be achievable by systemic administration. Localized drug delivery may be achieved, for example, by coating balloon catheters, stents and the like with the therapeutic agent to be locally delivered. The coating on medical devices may provide for controlled release, which may include long-term or sustained release, of a bioactive material.
Aside from facilitating localized drug delivery, medical devices may be coated with materials to provide beneficial surface properties. For example, medical devices are often coated with radiopaque materials to allow for fluoroscopic visualization while placed in the body. It is also useful to coat certain devices to achieve enhanced biocompatibility and to improve surface properties such as lubriciousness.
Coatings have been applied to medical devices by processes such as dipping, spraying, vapor deposition, plasma polymerization, spin-coating and electrodeposition. Although these processes have been used to produce satisfactory coatings, they have numerous, associated potential drawbacks. For example, it may be difficult to achieve coatings of uniform thicknesses, both on individual parts and on batches of parts. Further, many conventional processes require multiple coating steps or stages for the application of a second coating material, or may require drying between coating steps or after the final coating step.
The spray-coating method has been used because of its excellent features, e.g., good efficiency and control over the amount or thickness of coating. However, conventional spray-coating methods, which may be implemented with a device such as an airbrush, have drawbacks. For example, when a medical device has a structure such that a portion of the device obstructs sprayed droplets from reaching another portion of the device, then the coating becomes uneven. Specifically, when a spray-coating is employed to coat a stent having a tube-like structure with openings, such as stents described in U.S. Pat. Nos. 4,655,771 and 4,954,126 to Wallsten, the coating on the inner wall of the tube-like structure may tend to be thinner than that applied to the outer wall of the tube-like structure. Hence, conventional spraying methods may tend to produce coated stents with coatings that are not uniform. Furthermore, conventional spraying methods are inefficient. In particular, generally only 5% of the coating solution that is sprayed to coat the medical device is actually deposited on the surface of the medical device. The majority of the sprayed coating solution may therefore be wasted.
In the spin-dipping process, a medical device is coupled to a spinning device, and then, while rotating about a central axis, the medical device is dipped into a coating solution to achieve the desired coating. This process also suffers from many inefficiencies including the unevenness of the coated layer and a lack of control over the coated layer's thickness.
In addition to the spray coating and spin-dipping methods, the electrostatic deposition method has been suggested for coating medical devices. For example, U.S. Pat. Nos. 5,824,049 and 6,096,070 to Ragheb et al. mention the use of electrostatic deposition to coat a medical device with a bioactive material. In the conventional electrodeposition or electrostatic spraying method, a surface of the medical device is electrically grounded and a gas may be used to atomize the coating solution into droplets. The droplets are then electrically charged using, for example, corona discharge, i.e., the atomized droplets are electrically charged by passing through a corona field. Since the droplets are charged, when they are applied to the surface of the medical device, they will be attracted to the surface since it is grounded.
One disadvantage of conventional electrostatic spraying is that it requires a complicated spraying apparatus. In addition, because conventional electrostatic systems use a gas to move the droplets from a source to a target, controlling the gas pressure is crucial for accurate coating. However, it is not easy to control the gas pressure so that the target surface is evenly and sufficiently coated without losing much of the coating solution.
Another method of coating a device can be achieved with electrohydrodynamic spraying. Using this method, a gas is not needed to disperse the coating. Electrohydrodynamic coating is accomplished by forcing a compatible solution through a nozzle assembly that has been electrically charged. The coating solution passes through the charged nozzle where it is electrically charged. As the solution exits the nozzle, the solution atomizes as the charged particles repel each other. This action forms the spray mist. The charged particles are attracted to the device to be coated when the device is connected to an electrical ground.
Devices may be coated by a gas assisted spraying process. A polymer/drug combination may be dissolved in a solvent mixture. The solution may be sprayed onto the devices and a polymer/drug film may be formed when the solvents evaporate. The ability to apply thin coatings on products may be limited by the capabilities of a gas assisted spraying process. The coating may flow on the medical device prior to drying, thereby creating an uneven concentration of bioactive agent on the surface of the device. A gas assisted spraying process may have a high variability for thin coatings.
Conventional methods of coating stents or devices with a drug-polymer layer, such as spraying or dipping, may require a solution of the drug-polymer to physically wet the surface of the stent. Spraying or dipping may cause uneven and unpredictable wetting, and distribution and evaporation of the solvent molecules may result in a non-uniform coating. The drying of the coating may lead to cracking and/or points of stress in the coating. A non-uniform coating may lead to the unit failing agent release requirements, drug uniformity and coating thickness specifications.
During deployment and loading of self-expanding (SE) stents, there may be significant friction between the stent surface and the sheath. Longer stents may have higher friction forces. These shear forces may be especially damaging in relation to coated SE stents. As the application of drug eluting coatings allows the use of longer stents, the problems resulting from this frictional interaction may increase. Similarly, during deployment of balloon-expandable stents, there may be a significant friction between the unfolding balloon and the stent surface.
Additionally, due to the large weight of a stent in relation to a coating weight (with SIBS\paclitaxel coating weight to stent weight having a ratio of approximately 1 to 1000), it may be difficult to measure the exact amount of drug coating on a stent.
Furthermore, due to the complex shape of a stent, it may be difficult to produce a homogeneous uniform coating on the stent surface. Similarly, the deposition of a drug coating that has a predefined pattern over the stent surface (for example, a 20% increased drug concentration at both ends of the stent in order to anticipate edge effects) may be difficult.
There is, therefore, a need for a cost-effective method of linking drug release coatings to the medical device which is not sensitive to the loading and deployment forces. The method should assure defect-free coatings and uniform drug dose per unit device. The method would provide better control of the agent release profile of the device, including increasing or decreasing the release of the bioactive agent. The method would also improve the quality of the coating of the device by allowing drug concentration variations as well as different drugs on different parts of the device. The method would thus allow for better control of the sensitivity of the bioactive material and would reduce variations in the coating properties. Each of the references cited herein is incorporated by reference herein for background information.